SUMMARY OF WORK A. To determine whether ischemic ST segment changes occurring only during recovery from maximal treadmill exercise predict future coronary events (CE) in clinically healthy populations, we compared 2 groups of BLSA subjects: 150 with 1mm ST segment depression occurring during exercise (Group 1) and 64 with such ST changes limited only to recovery (Group 2). The 2 groups were similar in age, gender, and coronary risk factors. Over a mean follow-up of 9.1 years, CE (angina pectoris, myocardial infarction or coronary death) developed in 14.6% of Group 1 and 18.7% of Group 2, p=NS. By logistic regression analyses older age, higher serum cholesterol and ischemic ST segment depression (whether during exercise or limited to recovery) were independent predictors of future CE. B. To investigate whether chronic endurance training is protective against the development of exercise-induced silent myocardial ischemia, we performed maximal treadmill exercise tests with tomographic thallium scanning in 70 male master athletes aged 63?6 years and 85 healthy untrained men of similar age. The prevalence of concordant exercise-induced ST-segment depression on ECG and thallium perfusion abnormalities was 16% in athletes and 21% in control men, p=NS. Although hypertension, abnormal serum lipids or diabetes were not present in any athletes, the apolipoprotein E4A allele was found in 9 of 11 athletes with silent ischemia versus only 2 of 32 with normal exercise tests, p<0.0001). Thus, exercise-induced silent myocardial in older male athletes occurs with a frequency similar to that in untrained men and is strongly associated with the E4 allele. C. We evaluated whether a positive relationship exists between increased intimal-medial thickness (IMT) of the common carotid artery (CCA) and subclinical coronary artery disease (CAD) similar to that documented for symptomatic CAD. In 469 BLSA volunteers, by multiple regression analysis, IMT was best explained by age (p<0.0001), CCA diameter (p<0.001),systolic blood pressure (p<0.001), possible CAD (p<0.01) and manifest CAD (p<0.0001). Subjects with asymptomatic exercise-induced ST segment depression combined with a reversible thallium perfusion defect had IMT values virtually identical to those in patients with clinically manifest CAD.